Experiments are proposed to elucidate cellular mechanism by which selective innervation patterns in the mammalian CNS evolve from initially more widespread projections through axonal remodelling. The ontogeny of retinotopic order and radial stratification of the retinal projection to the superior colliculus of the mouse will be studied by anatomical mapping and characterization of individual optic arborizations using horseradish peroxidase as a tracer. Developmental transformations in the retinal projection, already identified in preliminary work, will be correlated with other major cellular events through quantitative studies of normal neuron death in the retina and colliculus and of synapse formation and dendritic elaboration in the colliculus. Potential controls on and functions of axonal remodelling may thus be identified for future research. In addition to this descriptive work, evaluation of particular mechanisms will be done through the study of perturbed development. An experiment is proposed to determine if an abnormal laminar distribution of optic axons recently discovered in the reeler mutant mouse derives from a defect in normal axonal remodelling. The consequences of aberrant axon trajectories for the formation of appropriate stratified connectivity patterns with target cell classes will be studied with peroxidase tracing and combined Golgi-electron microscopic methods. Results are expected to bear on the relative roles of axon pathway guidance and chemospecific recognition mechanisms in the formation of selective connections. Finally, the role of axon-axon competition will be investigated using a neuroplasticity paradigm in hamsters, which are more immature at birth than hamsters. Unilateral collicular lesions in newborns result in both eyes projecting to the remaining colliculus. The effect of transient colchicine-blockade of axon transport in one eye on the establishment of segregated territories will be determined using anterograde tracing methods. An expanded territory taken by the untreated projection would be consistent with the hypothesis that axonal arborization progresses in response to target sprouting factors until they become neutralized or turned off by axonally-transported agents. This work should contribute to an understanding of general developmental principles relevant to the prediction of compensatory responses of the developing human CNS to damage.